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Gene Alterations for Cystic Fibrosis May Also Account for Chronic Sinus
Problems in Some

Gene alterations known to cause the inherited disorder cystic fibrosis (CF),
which is characterized by mucous membrane abnormalities in the lungs, appear
also to contribute to chronic sinus problems in some people, according to a
report in this week's Journal of the American Medical Association. About 14
percent of the general U.S. population suffers from chronic sinusitis, a
persistent and often painful inflammation of the mucous membranes in the
sinus cavities around the nose and eyes and forehead. The disease occurs
frequently in patients with asthma and also in people with allergic
rhinitis.

"The study is among the first to investigate the genetic basis of chronic
sinusitis, a common and troublesome disorder. It provides new insights into
the cause of the disease in some people and points to new strategies for
diagnosis and treatment," says Marshall Plaut, M.D., of the National
Institute of Allergy and Infectious Diseases (NIAID). "It represents a new
and important research direction."

The study was supported by NIAID, the National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Center for Research
Resources, all components of the National Institutes of Health (NIH). The
Cystic Fibrosis Foundation also supported the research.

Because chronic sinusitis occurs commonly in people with CF, a disorder now
diagnosed by the presence of alterations in a gene known as CFTR, Garry
Cutting, M.D., and his colleagues at the Johns Hopkins University in
Baltimore, wanted to know if changes in the CFTR gene might also play a role
in sinusitis in people who don't have CF. So they compared the DNA of 147
patients with sinusitis, who came to their ear-nose-and-throat clinic, to
that of 123 people without sinusitis. Patients with cystic fibrosis were
excluded from the study.

CFTR's usual job is to regulate the flow of salt and water across the cell
membrane. People with cystic fibrosis carry two copies of an altered CFTR
gene, which affects the membranes in the lungs and leads to accumulation of
thick, sticky mucous that is not only difficult to clear, but also provides
a breeding ground for bacteria.

"Certainly many things contribute to chronic sinusitis in people who have no
known family history of cystic fibrosis," says Dr. Cutting. "But we
wondered if at least some sinusitis sufferers in the general population
might also carry a variant of one copy of the CFTR gene that contributes to
their sinusitis but spares them of cystic fibrosis."

CFTR gene alterations associated with CF occur in about 3.6 percent in the
general population. Analysis of the DNA samples from the patient volunteers
revealed CF mutations in the CFTR gene in 10 of the 147 volunteers who had
chronic sinusitis but not CF. Each of the sinusitis sufferers had
characteristic thickening of the mucous membranes in their noses or sinuses.
The results showed the sinusitis sufferers were nearly five times more
likely than their healthy counterparts to carry a CFTR alteration associated
with CF. Of the 10 patients who did have CF-linked alterations, 9 also
carried another CFTR variant known as M470V, which occurs in about 50
percent of the general population.

In recent years, chronic sinusitis has accounted for over 11 million visits
to doctors' offices. Often, the condition can be controlled with
decongestants, antihistamines, and nasal corticosteroid sprays and sometimes
antibiotics. Several of the patients in Dr. Cutting's study had also
received sinus surgery multiple times. Yet even those efforts fail to
relieve the condition in some patients.

NIAID is a component of the NIH. NIAID supports basic and applied research
to prevent, diagnose and treat infectious and immune-mediated illnesses,
including HIV/AIDS and other sexually transmitted diseases, tuberculosis,
malaria, autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.

The National Institute of Allergy and Infectious Diseases
is a component of the National Institutes of Health,
U.S. Department of Health and Human Services.

Reference:
XJ Wang et al. Mutation in the gene responsible for cystic fibrosis and
predisposition to chronic rhinosinusitis in the general population. JAMA
284(14):1814-1819 (2000).